The primary objective of this research proposal is to determine molecular basis for the involvement of (Na ion plus K ion)-ATPase in the pharmacological and toxicological actions of cardiac glycosides. Several hoomones such as thyroxine, gluco- and mineralocorticoids, insulin, and catecholamines have been implicated in the regulation of (Na ion plus K ion)-ATPase. Therefore, another objective of this research program is to explore molecular mechanisms involved in the regulation of monovalent cation transport system by some selected hormones. This research plan is divided into five sections, each dealing with some aspect of (Na ion plus K ion)-ATPase. The first attempts to delineate the involvement of (Naion plus Kion)-ATPase in the inotropic effects of cardiac glycosides. The second and third examines the hypothesis that inhibition of (Na ion plus K ion)-ATPase in the sympathetic nerve endings, may be involved in part, in the arrhythmogenic actions of cardiac glycosides. In addition, these two sections deal with the participation of (Na ion plus K ion)-ATPase in the norepinephrine uptake or release at the cardiac and other peripheral organ's sympathetic nerve endings. The fourth section describes a study of the regulation of (Na ion plus K ion)-ATPase by mineralocorticoids and thyroid hormones. The fifth section deals with the involvement of (Na ion plus K ion)-ATPase in the spontaneous fibrillation of chronically denervated mammalian skeletal muscle and the regulation of cation transport in the denervated muscle by catecholamines, insulin, and thyroid hormones.